On June 22, 2020 Myovant Sciences (NYSE: MYOV), a healthcare company focused on redefining care for women and for men, reported that its New Drug Application (NDA) for once-daily, oral relugolix (120 mg) for the treatment of men with advanced prostate cancer has been accepted for Priority Review by the U.S. Food and Drug Administration (FDA) (Press release, Myovant Sciences, JUN 22, 2020, https://investors.myovant.com/news-releases/news-release-details/myovant-sciences-announces-priority-review-and-fda-acceptance [SID1234561327]).

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"We are delighted that the FDA has accepted for Priority Review our New Drug Application for relugolix, bringing us one step closer to providing a one pill, once a day potential new treatment option to men with advanced prostate cancer," said Lynn Seely, M.D., chief executive officer of Myovant Sciences. "As recently published in the New England Journal of Medicine, relugolix demonstrated superior efficacy and a 54% lower risk of major adverse cardiovascular events compared to the current standard of care, leuprolide acetate injections, in the Phase 3 HERO study."

The FDA grants Priority Review to applications for potential therapies that, if approved, would be significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions when compared to standard applications. The FDA has set a target action date of December 20, 2020 under the Prescription Drug User Fee Act (PDUFA). In its acceptance letter, the FDA also stated that it is currently not planning to hold an advisory committee meeting for this application. If approved, relugolix would be the first and only oral gonadotropin-releasing hormone (GnRH) receptor antagonist treatment for men with advanced prostate cancer.

In May 2020, Myovant submitted a separate NDA for once-daily, oral relugolix combination tablet (relugolix 40 mg, estradiol 1.0 mg, and norethindrone acetate 0.5 mg) for women with heavy menstrual bleeding associated with uterine fibroids. A Marketing Authorization Application for relugolix combination tablet in women with moderate to severe symptoms associated with uterine fibroids is also under review by the European Medicines Agency.

About the Phase 3 HERO Program in Advanced Prostate Cancer
Myovant’s Phase 3 clinical program for advanced prostate cancer consisted of a randomized, open-label, parallel-group, multinational clinical study designed to evaluate the safety and efficacy of relugolix in over 900 men with androgen-sensitive advanced prostate cancer who required at least one year of continuous androgen deprivation therapy. Men were randomized 2:1 to receive a single loading dose of relugolix 360 mg followed by relugolix 120 mg once daily, or to treatment with leuprolide acetate 3-month depot injection, respectively.

Relugolix met the primary efficacy endpoint, with 96.7% of men treated with relugolix achieving sustained testosterone suppression to castrate levels (< 50 ng/dL) through 48 weeks versus 88.8% of men treated with leuprolide acetate. Relugolix also met all six key secondary endpoints, demonstrating superiority to leuprolide acetate in rapid and profound suppression of testosterone and PSA response, in addition to improved testosterone recovery after discontinuation of treatment. Men in the relugolix group had a 54% lower risk of major adverse cardiovascular events (MACE) compared to men in the leuprolide acetate group (2.9% vs. 6.2%, respectively). In men with a reported history of MACE, the relugolix group had 80% fewer MACE events reported compared to the leuprolide acetate group (3.6% vs. 17.8%, respectively). The overall incidence of adverse events in the relugolix and leuprolide acetate groups was comparable (92.9% vs. 93.5%, respectively).

Data from an additional key secondary endpoint, castration resistance-free survival, are expected in the third quarter of 2020.

About Prostate Cancer
Prostate cancer is the second most prevalent form of cancer in men and the second leading cause of death due to cancer in men in the U.S. Cardiovascular mortality is the leading cause of death in men with prostate cancer and accounts for 34% of deaths in men with prostate cancer in the U.S. More than three million men in the U.S. are currently living with prostate cancer, and approximately 190,000 men are estimated to be newly diagnosed in 2020. Advanced prostate cancer is prostate cancer that has spread or come back after treatment and may include men with biochemical recurrence (rising PSA in the absence of metastatic disease on imaging), locally advanced disease, or metastatic disease. Front-line medical therapy for advanced prostate cancer typically involves androgen deprivation therapy, which reduces testosterone to very low levels, commonly referred to as castrate levels. GnRH receptor agonists, such as leuprolide acetate, are depot injections and the current standard of care for androgen deprivation therapy. However, GnRH receptor agonists may be associated with mechanism-of-action limitations, including the potentially detrimental initial surge in testosterone levels that can exacerbate clinical symptoms, which is known as clinical or hormonal flare, and delayed testosterone recovery after the drug is discontinued. Approximately 210,000 men are treated with androgen deprivation therapy with a GnRH agonist or antagonist each year.

About Relugolix
Relugolix is a once-daily, oral gonadotropin-releasing hormone (GnRH) receptor antagonist that reduces production of testicular testosterone, a hormone known to stimulate the growth of prostate cancer, and ovarian estradiol, a hormone known to stimulate the growth of uterine fibroids and endometriosis. Myovant is developing relugolix as a monotherapy tablet (120 mg once daily) for men with advanced prostate cancer. Myovant is also developing a relugolix combination tablet (relugolix 40 mg, estradiol 1.0 mg, and norethindrone acetate 0.5 mg) for women with uterine fibroids and for women with endometriosis.

On June 22, 2020 Provectus (OTCQB: PVCT) reported that data from ongoing preclinical study of investigational autolytic cancer immunotherapy PV-10 (rose bengal disodium) is being presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2020 Virtual Annual Meeting II, held online June 22-24, 2020 (Press release, Provectus Biopharmaceuticals, JUN 22, 2020, View Source [SID1234561326]). This PV-10 research has been led by Aru Narendran, MD, PhD and his team of researchers at the University of Calgary in Alberta, Canada (UCalgary).

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Dr. Narendran and his colleagues studied the effects of PV-10 treatment on primary cells and cell lines derived from pediatric leukemia patients. UCalgary showed that PV-10 treatment led to STING dimerization and the release of interferon gamma (IFNγ), indicating a potential immune activation mechanism of PV-10. UCalgary further showed that heat shock proteins (HSPs), which chaperone misfolded or abnormally folded proteins, associated with STING dimerization in PV-10-treated cells, indicating a mechanism that may lead to enhanced STING activation following PV-10 treatment.

A copy of the AACR (Free AACR Whitepaper) poster presentation is available on Provectus’ website at View Source

"The essence of cancer is the struggle for survival of these abnormal cells in the body. Over the course of their existence, cancer cells acquire multiple cellular pathways that become active or inactive in order for cancer to have a survival advantage against our immune system. This struggle changes the biology of cancer cells, which may have a direct impact on the activity of anticancer drugs within these cells," Dr. Narendran said. "We observed these very dynamics from our research on PV-10 and pediatric leukemia cells. Classic STING activation does not occur through PV-10 treatment. Rather, STING forms a dimer complex following PV-10 treatment, which may potentially lead to effective immune activation and anticancer activity."

Dr. Narendran added, "Our PV-10 research has enabled us to show, we believe for the first time, that heat shock proteins, which play important roles in the survival of cancer cells, are involved in STING activation. We also believe the involvement of heat shock proteins with STING is an important observation that requires further study."

Dominic Rodrigues, Vice Chair of Provectus’ Board of Directors, said "We are grateful to Dr. Narendran, his team, and the University of Calgary for their consequential research on PV-10 to better understand the basic biology of cancer. This seminal discovery of PV-10-induced alterations of the STING pathway, which plays a pivotal role in innate immunity, contributes to an increasing body of knowledge about how and why PV-10 may function as an immunotherapy across a growing number of cancer types."

About PV-10

By targeting tumor cell lysosomes, investigational new drug PV-10 treatment may yield immunogenic cell death in solid tumor cancers that results in tumor-specific reactivity in circulating T cells and a T cell mediated immune response against treatment refractory and immunologically cold tumors.1-3 Adaptive immunity can be enhanced by combining checkpoint blockade (CB) with PV-10.4

PV-10 is undergoing clinical study for adult solid tumor cancers, such as relapsed and refractory cancers metastatic to the liver and metastatic melanoma. PV-10 is also undergoing preclinical study for relapsed and refractory pediatric solid tumor cancers (e.g., neuroblastoma, Ewing sarcoma, rhabdomyosarcoma, and osteosarcoma)5,6 and relapsed and refractory pediatric blood cancers (such as acute lymphocytic leukemia and acute myelomonocytic leukemia)7,8.

Tumor Cell Lysosomes as the Seminal Drug Target

Lysosomes are the central organelles for intracellular degradation of biological materials, and nearly all types of eukaryotic cells have them. Discovered by Christian de Duve, MD in 1955, lysosomes are linked to several biological processes, including cell death and immune response. In 1959, de Duve described them as ‘suicide bags’ because their rupture causes cell death and tissue autolysis. He was awarded the Nobel Prize in 1974 for discovering and characterizing lysosomes, which are also linked to each of the three primary cell death pathways: apoptosis, autophagy, and necrosis.

Building on the Discovery, Exploration, and Characterization of Lysosomes

Cancer cells, particularly advanced cancer cells, are very dependent on effective lysosomal functioning.9 Cancer progression and metastasis are associated with lysosomal compartment changes10,11, which are closely correlated with (among other things) invasive growth, angiogenesis, and drug resistance12.

PV-10 selectively accumulates in the lysosomes of cancer cells upon contact, disrupting the lysosomes and causing the cells to die. Provectus1,13, external collaborators6, and other researchers14,15,16 have independently shown that PV-10 (RB) triggers each of the three primary cell death pathways: apoptosis, autophagy, and necrosis.

Cancer Cell Autolytic Death via PV-10: PV-10 induced autolytic cell death, or death by self-digestion, in Hepa1-6 murine hepatocellular carcinoma (HCC) cells can be viewed in this Provectus video of the event (ethidium homodimer 1 [ED-1] stains DNA, but is excluded from intact nuclei; lysosensor green [LSG] stains intact lysosomes; the video is provided in 30-second frames; the event has a duration of approximately one hour). Exposure to PV-10 triggers the disruption of lysosomes, followed by nucleus failure and autolytic cell death. Identical responses have been shown by the Company in HTB-133 human breast carcinoma (which can be viewed in this Provectus video; this event has a duration of approximately two hours) and H69Ar human multidrug-resistant small cell lung carcinoma. Cancer cell autolytic cell death was reproduced by research collaborators in neuroblastoma cells to show that lysosomes are disrupted upon exposure to PV-10.5

PV-10 causes acute autolytic destruction of injected tumors (i.e., cell death), mediating the release of danger-associated molecular pattern molecules (DAMPs) and tumor antigens that may initiate an immunologic cascade where local response by the innate immune system may facilitate systemic anti-tumor immunity by the adaptive immune system. The DAMP release-mediated adaptive immune response activates lymphocytes, including CD8+ T cells, CD4+ T cells, and NKT cells, based on clinical and preclinical experience in multiple tumor types. Mediated immune signaling pathways may include an effect on STING, which plays an important role in innate immunity8.

Orphan Drug Designations (ODDs)

ODD status has been granted to PV-10 by the U.S. Food and Drug Administration for the treatments of metastatic melanoma in 2006, hepatocellular carcinoma in 2011, neuroblastoma in 2018, and ocular melanoma (including uveal melanoma) in 2019.

Drug Product

Rose bengal disodium (RB) (4,5,6,7-tetrachloro-2’,4’,5’,7’-tetraiodofluorescein disodium salt) is a small molecule halogenated xanthene and PV-10’s active pharmaceutical ingredient. The Company manufactures RB using a patented process designed to meet stringent modern global quality requirements for pharmaceuticals and pharmaceutical ingredients (Good Manufacturing Practice, or GMP). PV-10 drug product is an injectable formulation of 10% w/v GMP RB in 0.9% saline, supplied in single-use glass vials containing 5 mL (to deliver) of solution, and administered without dilution to solid tumors via intratumoral injection.

Intellectual Property (IP)

Provectus’ IP includes a family of US and international (a number of countries in Asia, Europe, and North America) patents that protect the process by which GMP RB and related halogenated xanthenes are produced, avoiding the formation of previously unknown impurities that exist in commercial grade RB in uncontrolled amounts. The requirement to control these impurities is in accordance with International Council on Harmonisation (ICH) guidelines for the manufacturing of an injectable pharmaceutical. US patent numbers are 8,530,675, 9,273,022, and 9,422,260, with expirations ranging from 2030 to 2031.

The Company’s IP also includes a family of US and international (a number of countries in Asia, Europe, and North America) patents that protect the combination of PV-10 and systemic immunomodulatory therapy (e.g., anti-CTLA-4, anti-PD-1, and anti-PD-L1 agents) for the treatment of a range of solid tumor cancers. US patent numbers are 9,107,887, 9,808,524, 9,839,688, and 10,471,144, with expirations ranging from 2032 to 2035; US patent application numbers include 20200138942.

On June 22, 2020 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported preclinical data related to AUTO5 in T cell lymphoma and AUTO6NG in small cell lung cancer, as well as an oral presentation related to AUTO7 in prostate cancer at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II on June 22 – 24, 2020 (Press release, Autolus, JUN 22, 2020, View Source [SID1234561325]).

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"Behind our lead programs AUTO1 in ALL and AUTO3 in DLBCL, we have a number of exciting preclinical product candidates progressing towards the clinic," said Dr Christian Itin, chairman and chief executive officer of Autolus. "These data updates for AUTO5, AUTO6NG and AUTO7 illustrate the strength of our broad and modular cell programming technology to adapt the product properties to the specific tumor type."

"The Autolus R&D team is pleased to be presenting data updates across our preclinical pipeline, highlighting the strength of our in-house cell programming technology. The programs illustrate the utility of the technology for highly selective targeting with AUTO5 in T cell lymphoma as well as addressing the hostile solid tumor microenvironment with AUTO6NG and AUTO7 for the treatment of small cell lung cancer and prostate cancer, respectively," said Dr Martin Pulé, chief scientific officer and founder of Autolus. "We look forward to progressing these next generation preclinical programs into the clinic in 2021."

AUTO7: Anti-PSMA humanized CAR T cell with improved persistence and resistance to tumor microenvironment for metastatic castration resistant prostate cancer (mCRPC)
AUTO7 is a multi-modular CAR T cell program aimed at generating resilient CAR T cells that can withstand the hostile solid tumor microenvironment (TME). By introducing Autolus’ proprietary programming modules, the new data demonstrate a positive effect on tackling the complex tumor biology in a metastatic, castration-resistant prostate cancer setting. AUTO7 uses an optimized CAR to target cancer cells expressing PSMA, even at low levels, and includes four of Autolus’ suite of cell programming modules to overcome tumor defenses and enhance efficacy: the dSHP2 programming module shielding AUTO7 from checkpoint inhibition, the dominant negative TGFβRII module acting as a decoy for inhibitory TGFβ signaling, the IL7 chimeric cytokine receptor (CCR) module enhancing CAR T cell survival, and finally, a module that activates immune responses at the tumor site through limited secretion of IL-12. All programming modules provide their effect within the CAR T cell and the immediate surrounding environment, rather than having a systemic effect with its potential associated systemic toxicities.

The preclinical data presented by Autolus demonstrate that AUTO7 is highly potent in cytotoxicity assays against cells expressing PSMA, even at low levels, and demonstrate the feasibility of this multi-modular cell programming approach in overcoming the immunotherapeutic challenges presented by advanced prostate cancer, which is typically otherwise an immunologically cold tumor.

Oral Presentation Title: AUTO7: Anti-PSMA humanized CAR T cell with improved persistence and resistance to tumor microenvironment for metastatic castration resistant prostate cancer (mCRPC)
Session Title: Mini-symposium; MS.IM02.01 – Adoptive Cell Therapy
Abstract: 1070
Date & Time: June 23, 2020, 9:00 AM – 10:30 AM
Presenter: Dr Marco Della Peruta, Senior Scientist II, Immunobiology, Autolus Therapeutics

AUTO6NG overcomes immune suppressive mechanisms in the TME and demonstrate preclinical anti-tumor activity in GD2-expressing solid tumors
AUTO6 is a GD2-targeting CAR T candidate, developed in collaboration with UCL, that has been shown to be clinically active in neuroblastoma.* GD2 has been evaluated and validated as an attractive CAR T target antigen in small cell lung cancer (SCLC). AUTO6 alone has demonstrated efficacy in an in vitro SCLC model, but successful tumor targeting alone was not sufficient to drive in vivo efficacy in the same SCLC model. Autolus has designed enhancing modules to specifically overcome TME defenses in solid tumor settings. In addition to the original AUTO6 GD2 CAR and safety switch, the company has tested the impact of adding its dSHP2 module, its dominant negative TGFβRII module and its IL7 CCR module, as described above. Autolus has presented new preclinical data demonstrating the validity of GD2 as a CAR T target in SCLC and the ability of these efficacy-enhancing modules to drive in vivo efficacy in an SCLC mouse model. The new data presented by Autolus suggest that AUTO6NG can overcome the immune suppressive mechanisms in the TME.

*AACR 2018 presentation of AUTO6 clinical data, Dr Karin Straathof, UCL

Poster Presentation Title: AUTO6NG overcomes immune suppressive mechanisms in the TME and demonstrate preclinical anti-tumor activity in GD2-expressing solid tumors
Poster Session Title: Poster Session; PO.TB06.05 – Immune Cells in the Tumor Microenvironment 2
Poster: 2661 / 9
Date & Time: June 22, 2020, 9:00 AM – 6:00 PM
Presenter: Dr Muhammad Al-Hajj, Senior Vice President, Head of Translational Medicine, Autolus Therapeutics

AUTO5: Targeting TRBC2 for the treatment of T cell lymphomas
There is currently no approved programmed T cell therapy available as a stand-alone treatment for T cell lymphomas. AUTO4 is the company’s TRBC1 CAR T cell candidate aimed at targeting TRBC1+ patients (approximately 40% of the T cell lymphoma population). AUTO5, a novel CAR T candidate targeting the TRBC2+ population, is designed to capture the remaining 60% of the T cell lymphoma population. Autolus has presented data showing that AUTO5 is able to selectively target TRBC2+ and spare TRBC1+ cells in a mixed healthy peripheral blood mononuclear cells (PBMC) population. The company demonstrates that its novel anti-TRBC2 binder incorporated in a second-generation CAR with optimized architecture can selectively kill TRBC2+ T cells of healthy PBMC donors. Alongside the killing efficiency, AUTO5 is also capable of specific cytokine release and proliferation in response to interaction with TRBC2 target cells. The same specific killing effect was observed in vivo when mice were challenged in a co-infused mixed TRBC1/TRBC2 tumor model. The anti-TRBC2 CAR was able to clear the TRBC2+ T cells, while sparing the TRBC1+ T cell population. These data highlight the specificity and selectivity of the company’s T-cell lymphoma product candidate, AUTO5.

Poster Presentation Title: Targeting TRBC1 and 2 for the treatment of T cell lymphomas
Poster Session Title: Poster Session; PO.IM02.02 – Adoptive Cell Therapy 2
Poster: 2183 / 15
Date & Time: June 22, 2020, 9:00 AM – 6:00 PM
Presenter: Dr Mathieu Ferrari, Associate Director of Binder Discovery, Autolus Therapeutics

Investor call on Thursday, June 25, 2020
Management will host a conference call and webcast at 8:30 AM EDT/1:30 PM BST to discuss the AACR (Free AACR Whitepaper) data. To listen to the webcast and view the accompanying slide presentation, please go to: View Source

The call may also be accessed by dialing (866) 679-5407 for U.S. and Canada callers or (409) 217-8320 for international callers. Please reference conference ID 1866794. After the conference call, a replay will be available for one week. To access the replay, please dial (855) 859-2056 for U.S. and Canada callers or (404) 537-3406 for international callers. Please reference conference ID 1866794.

On June 22, 2020 DelMar Pharmaceuticals, Inc. (Nasdaq: DMPI) ("DelMar" or the "Company"), a biopharmaceutical company focused on the development of new solid tumor cancer therapies, reported positive interim data from its two Phase 2 trials of VAL-083 for the treatment of glioblastoma multiforme (GBM) demonstrating improved outcomes over current standard of care as both a first-line treatment and for recurrent GBM (Press release, DelMar Pharmaceuticals, JUN 22, 2020, View Source;diagnosed-and-recurrent-gbm-at-the-aacr-virtual-annual-meeting-ii [SID1234561324]). The data, presented in two posters at the 2020 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II, support the Company’s planned participation in the Global Coalition for Adaptive Research’s (GCAR) Glioblastoma Adaptive Global Innovative Learning Environment (GBM AGILE) clinical trial. DelMar previously announced its invitation from GCAR to participate in the selective GBM AGILE study. This pivotal study, with its robust trial design, industry leading partners, and strong regulatory endorsement, is intended to serve as the basis for VAL-083’s new drug application (NDA) submission and registration.

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Dr. John de Groot, Chairman of the Department of Oncology at MD Anderson Cancer Center and planned Principal Investigator for the VAL-083 arm of the GCAR GBM AGILE registration study, noted, "These data continue to demonstrate an improvement over the historical outcomes of standard therapy and validate VAL-083’s inclusion in a more robust setting as part of the GBM AGILE study. In MD Anderson’s Glioblastoma Moon Shots Program, we are looking to create giant leaps to help patients with GBM where treatment options are limited. It is our hope that VAL-083 may serve as an important new therapy to help physicians and patients dramatically reduce mortality and suffering due to this deadly cancer. We continue to be encouraged by these results and are excited by the opportunity to collaborate with DelMar and GCAR to further explore the potential of VAL-083."

Interim outcomes included:

Poster #CT273 – "Phase 2 study of dianhydrogalactitol (VAL-083) in patients with newly diagnosed MGMT-unmethylated glioblastoma"

Results:

For the 25 patients initially receiving the treatment dose that will be carried forward in the GBM AGILE pivotal study (30 mg/m2/day on days 1, 2 and 3 of a 21-day cycle) median progression-free survival (PFS) was reported to be 8.7 months (confidence interval, or CI 6.0-12.0 months) as of the May 15, 2020 cut-off date.
Overall PFS (n=29) with VAL-083 was 8.7 months (CI 6.4-11.2 months).
While not a head-to-head trial, historically temozolomide (TMZ), the standard of care, has been demonstrated to have 6.9 months PFS in newly_diagnosed unmethylated GBM patients.
The open-label Phase 2 study in newly-diagnosed unmethylated GBM is being conducted at Sun Yat-sen University Cancer Center in China. The Company announced full enrollment of the study on February 19, 2020.

Poster #CT272 – "Phase 2 study of dianhydrogalactitol (VAL-083) in patients with MGMT-unmethylated bevacizumab-naïve glioblastoma in the recurrent of adjuvant setting"

Results:

In recurrent GBM, for the 37 patients initially receiving the intended treatment dose that will be carried forward in the GBM AGILE pivotal study (30 mg/m2/day on days 1, 2 and 3 of a 21-day cycle), median overall survival (mOS) is currently 8.5 months (CI 5.7-14.3 months) as of the May 28, 2020 cut-off date.
Overall mOS for the 72 patients who have completed at least one cycle of treatment was 7.1 months (CI 5.8-9.9 months).
While this is not a head-to-head trial, historically lomustine, which is the most commonly used chemotherapy for these patients, has demonstrated a mOS of 7.2 months in recurrent unmethylated GBM patients.
In the adjuvant setting, patients receive VAL-083 as adjuvant therapy following treatment with radiation and TMZ. As of the data cut-off date of May 28, 2020, 19 evaluable subjects have completed at least one 21-day cycle of treatment, with a total of 25 subjects enrolled. Enrollment for this arm was initiated in July 2019, and all 25 subjects enrolled to-date were alive at the data cut-off date.
Based on encouraging outcomes, the Company plans to increase the adjuvant arm from the originally planned 24 patients to include up to 12 additional patients.
The open-label Phase 2 study in recurrent and adjuvant unmethylated GBM is being conducted at M.D. Anderson Cancer Center in Houston.

Dr. Barbara O’Brien, Principal Investigator, commented, "These results continue to demonstrate the promise of VAL-083, along with a very favorable safety profile in both the adjuvant and recurrent settings. Further, we are excited to be able to add additional patients to the adjuvant arm of the study, which has received great interest from patients, and has enrolled faster than predicted. VAL-083 is well tolerated by these patients and extending the study provides an opportunity for patients to have access to this important trial for glioblastoma."

Similar to prior experience with VAL-083, myelosuppression has been the most common adverse event observed. Three subjects experienced a serious adverse event (SAE), possibly related to VAL-083 in the newly-diagnosed group, while 10 subjects have experienced a possibly drug-related SAE in the recurrent group, and one patient has experienced a possibly drug-related SAE in the adjuvant group as of the relevant data cut-off dates.

Saiid Zarrabian, CEO of DelMar Pharmaceuticals, added, "We continue to be encouraged with the interim outcomes for both of our ongoing Phase 2 trials of VAL-083 in GBM. With the support of these findings, we have commenced preparations for VAL-083’s participation in the GCAR pivotal GBM AGILE study. We look forward to reporting top-line results for the newly diagnosed Phase 2 study in the third quarter of 2020 and providing additional updates on both studies at the Society for Neuro-Oncology Annual Scientific Meeting in November 2020."

On June 22, 2020 Ayala Pharmaceuticals, Inc. (Nasdaq: AYLA), a clinical-stage oncology company focused on developing and commercializing small molecule therapeutics for patients suffering from rare and aggressive cancers, primarily in genetically defined patient populations, reported financial results for the first quarter ended March 31, 2020 and highlighted recent progress and upcoming milestones for its pipeline programs (Press release, Ayala Pharmaceuticals, JUN 22, 2020, View Source [SID1234561323]).

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"Despite the challenges presented by the COVID-19 pandemic, Ayala continues to operate from a position of strength both clinically and operationally. We remain on track to report additional data from our ongoing Phase 2 ACCURACY study in R/M ACC and to initiate our Phase 2 AL101 study of TNBC before year end," said Roni Mamluk, Ph.D., Chief Executive Officer of Ayala. "In addition, in May 2020, we completed our upsized IPO, providing us the financial stability to further develop both AL101 and AL102 across a wide range of genetically defined cancer indications, as well as in multiple myeloma in collaboration with Novartis."

Key Business and Clinical Highlights

Completed Upsized Initial Public Offering: In May 2020, Ayala successfully completed its initial public offering (IPO) of 3,666,667 shares of common stock and additional 274,022 shares in connection with the partial exercise of the underwriters’ option to purchase additional shares, at a public offering price of $15.00 per share. The total gross proceeds from the IPO were approximately $59.1 million. Through this offering Ayala broadened its shareholder base with a number of U.S. healthcare dedicated funds.

Received Fast Track Designation for AL101 for the Treatment of Recurrent/Metastatic Adenoid Cystic Carcinoma (R/M ACC): In March 2020, Ayala received Fast Track designation from the U.S. Food and Drug Administration (FDA) for AL101 for the treatment of R/M ACC with Notch-activating mutations. Ayala’s lead product candidate, AL101 is a potent, selective, injectable small molecule gamma secretase inhibitor (GSI) and was granted Orphan Drug Designation in May 2019 for the treatment of R/M ACC.

Commenced Dosing of Patients in 6mg Cohort of R/M ACC Study: Ayala commenced dosing of the second patient cohort in its ACCURACY study for the treatment of R/M ACC with Notch-activating mutations at the higher dose of 6mg. In the first cohort of the study, 45 patients were dosed at 4mg where clear signs of clinical activity were observed along with a favorable safety profile. The study is expected to dose 42 patients in the 6mg cohort.

Investigational New Drug (IND) Accepted by FDA for Phase 2 Study of AL101 For Treatment of TNBC: In April 2020, the FDA accepted the IND for the Phase 2 study of AL101 for treatment of triple negative breast cancer (TNBC.) The FDA approved the dosing to commence at 6mg in a monotherapy study to evaluate TNBC patients bearing Notch activating mutations who have undergone 3 prior lines of therapies or less.

Upcoming Milestones

On Track to Report Additional Phase 2 Data of AL101 in Patients with R/M ACC Data in The Second Half of 2020: Ayala plans to report additional data from its ongoing Phase 2 ACCURACY study of AL101 for the treatment of patients with R/M ACC with Notch-activating mutations, a rare malignancy of the secretory glands, at an upcoming medical meeting in the second half of 2020. Initial data demonstrating a 15% response rate and 69% disease control rate were previously reported out of the first 39 evaluable patients in the 4mg cohort.

On Track to Initiate Phase 2 Study of AL101 in Patients with Recurrent/Metastatic Triple Negative Breast Cancer (R/M TNBC) in The Second Half of 2020: Ayala plans to initiate a Phase 2 clinical trial of AL101 for the treatment of patients with R/M TNBC with Notch-activating mutations in the second half of 2020, subject to the impact of COVID-19.

First Quarter 2020 Financial Results

Cash Position: Cash and cash equivalents were $10.1 million as of March 31, 2020, as compared to $16.7 million as of December 31, 2019. Total cash, cash equivalents and marketable securities at March 31, 2020 did not include total net proceeds of approximately $55.0 million, after deducting underwriting discounts and commissions, from the Company’s IPO of 3,940,689 shares of common stock, including the partial exercise of the underwriters’ option to purchase additional shares, in May 2020. We expect the cash balance to fund operations into the second half of 2022 through potentially multiple key clinical and development milestones.

Collaboration Revenue: Collaboration revenue was $1.0 million for the first quarter of 2020, compared to $0.3 million for the same period in 2019. The increase in revenue was due to the advancement of our collaboration with Novartis on AL102 in combination with Novartis’ anti BCMA agent.

R&D Expenses: Research and development expenses were $5.1 million for the first quarter of 2020, compared to $2.8 million for the same period in 2019. The increase was primarily driven by higher costs related to the advancement of our ongoing Phase 2 study of AL101 in ACC and preparations for the initiation of the Phase 2 study in our TNBC trial.

G&A Expenses: General and administrative expenses were $1.3 million for the first quarter of 2020, compared to $0.8 million for the same period in 2019. The increase was primarily related to higher professional services and personnel costs to support the growth of the company.

Net Income/Loss: Net loss was $6.6 million, or $1.32 loss per share, for the first quarter of 2020, compared to $3.5 million, or $0.71 loss per share, for the same period in 2019, attributable mainly to the increase in our clinical operations.